Alternative polyadenylation-related genetic variants contribute to bladder cancer risk

Aberrant alternative polyadenylation(APA)events play an important role in cancers,but little is known about whether APA-related genetic variants contribute to the susceptibility to bladder cancer.Previous genome-wide association study performed APA quantitative trait loci(apaQTL)analyses in bladder cancer,and identified 17955 single nucleotide polymorphisms(SNPs).We found that gene symbols of APA affected by apaQTL-associated SNPs were closely correlated with cancer signaling pathways,high mutational burden,and immune infiltration.Association analysis showed that apaQTL-associated SNPs rs34402449 C>A,rs2683524 C>T,and rs11540872 C>G were significantly associated with susceptibility to bladder cancer(rs34402449:OR=1.355,95%confidence interval[CI]:1.159-1.583,P=1.33×10^(−4);rs2683524:OR=1.378,95%CI:1.164-1.632,P=2.03×10^(−4);rs11540872:OR=1.472,95%CI:1.193-1.815,P=3.06×10^(−4)).Cumulative effect analysis showed that the number of risk genotypes and smoking status were significantly associated with an increased risk of bladder cancer(P_(trend)=2.87×10^(−12)).We found that PRR13,being demonstrated the most significant effect on cell proliferation in bladder cancer cell lines,was more highly expressed in bladder cancer tissues than in adjacent normal tissues.Moreover,the rs2683524 T allele was correlated with shorter 3′untranslated regions of PRR13 and increased PRR13 expression levels.Collectively,our findings have provided informative apaQTL resources and insights into the regulatory mechanisms linking apaQTL-associated variants to bladder cancer risk.

CPPU may induce gibberellin-independent parthenocarpy associated with PbRR9 in‘Dangshansu’pear

Parthenocarpy is a valuable trait in self-incompatible plants,such as pear.N-(2-chloro-4-pyridyl)-N’-phenylurea(CPPU),a synthetic cytokinin analog,can induce parthenocarpy in pear(Pyrus spp.),but the mechanism of induction is unclear.To investigate the role of gibberellin in CPPU-induced parthenocarpy in pear,CPPU supplemented with paclobutrazol(PAC)was sprayed onto‘Dangshansu’pear.We found that the fruit set rate of pear treated with CPPU supplemented with PAC was identical to that in a CPPU-alone treatment group.In regard to cell development,CPPU mainly promoted hypanthium cell division and expansion,and PAC application had no influence on CPPU-induced cell development.RNA sequencing revealed that gibberellin 20 oxidase and gibberellin 3 oxidase genes were not differentially expressed following CPPU treatment.According to the analysis of fruit phytohormone content,the CPPU treatments did not induce gibberellin biosynthesis.These results suggest that CPPU-induced parthenocarpy may be gibberellin independent in‘Dangshansu’pear.After CPPU treatment,the indole acetic acid(IAA)content in fruit was significantly increased,and the abscisic acid(ABA)content was significantly decreased.Similarly,RNA sequencing revealed that many genes involved in the auxin and ABA pathways were significantly differentially expressed in the CPPU treatment groups;among them,indole-3-pyruvate monooxygenase(YUCCA)was significantly upregulated and 9-cis-epoxycarotenoid dioxygenase(NCED)was significantly downregulated.IAA and ABA may thus play important roles in CPPU-induced parthenocarpy.PbTwo-component response regulator9(PbRR9),PbYUCCA4,and PbNCED6 were then selected to further elucidate the mechanism of CPPU-induced parthenocarpy.A yeast one-hybrid assay indicated that PbRR9 can combine with the PbYUCCA4 and PbNCED6 promoters.Dual luciferase assays revealed that PbRR9 can promote and repress the activities of the PbYUCCA4 and PbNCED6 promoters,respectively.After the transient expression of PbRR9 in fruits,PbYUCCA4 expression was significantly upregulated,and PbNCED6 expression was significantly downregulated.This study uncovered a CPPU-induced parthenocarpy mechanism that is different from that in tomato.CPPU may upregulate PbYUCCA4 and downregulate PbNCED6 by upregulating PbRR9,thereby increasing IAA content and decreasing ABA content to ultimately induce parthenocarpy in‘Dangshansu’pear.However,because only a single time point was used and because‘botanical’and‘accessory’fruits have different structures,this conclusion is still preliminary.

Genetic variants in the Hedgehog signaling pathway genes are associated with gastric cancer risk in a Chinese Han population

The Hedgehog signaling pathway participates in the occurrence and progression of cancers including gastric cancer.We conducted this study to evaluate whether genetic variants in the Hedgehog signaling pathway genes would affect gastric cancer risk.Multi-marker Analysis of GenoMic Annotation(MAGMA)was used to investigate the aggregated genetic effects of single nucleotide polymorphisms(SNPs)assigned to candidate genes.The relationship between SNPs and gastric cancer risk was estimated by multivariate logistic regression analyses.Gene expression was calculated using databases obtained from The Cancer Genome Atlas(TCGA)and The Gene Expression Omnibus(GEO).Kaplan‐Meier plotter was used to evaluate the association between gene expression with gastric cancer survival.Tumor Immune Estimation Resource 2.0(TIMER 2.0)was applied to determine the correlation between selected gene expression and the immune cell infiltration degree.We identified that the G allele of rs2990912 in KIF27 was associated with higher gastric cancer risk,especially in the young and male subgroups.The expression of KIF27 in gastric cancer tissues was higher than that in normal tissues,leading to poor survival in gastric cancer patients.Besides,KIF27 expression was related to immune cell infiltration and positively correlated with PD-L1 expression.Our findings highlight the key role of genetic variation in the Hedgehog signaling pathway genes in gastric cancer susceptibility,which may provide important insights into the diagnosis,prognosis,and treatment of gastric cancer.